Arctiin Inhibits Cervical Cancer Cell Migration and Invasion through Suppression of S100A4 Expression via PI3K/Akt Pathway.

Chung-Yuan Lee,Pei-Ni Chen,Po-Hui Wang,Chiao-Wen Lin,Shun-Fa Yang,Min-Chieh Hsin,Yi-Hsuan Hsiao

doi:10.3390/pharmaceutics14020365

Abstract

Arctiin, a lignan glycoside, is isolated from Arctium lappa L. The anticancer effects of arctiin have been demonstrated in several studies. However, no research has been conducted on the anti-migration effect of arctiin in cervical cancer cells. The present study examined the effects of arctiin on cervical cancer cells and investigated the possible molecular mechanism. We demonstrated that arctiin exhibited low cytotoxicity and significantly inhibited cell migration and invasion in human cervical cancer cells. The S100A4 protein expression and mRNA levels were significantly reduced in HeLa and SiHa cells with arctiin treatment. Furthermore, silencing S100A4 by using small interfering RNA reduced cell migration, while overexpression of S100A4 mitigated the migration inhibition imposed by arctiin in cervical cancer cells. Western blotting revealed that arctiin significantly reduced phosphoinositide 3-kinase (PI3K) and phosphorylation of Akt in cervical cancer cells. Moreover, selective Akt induction by an Akt activator, SC-79, reverted cervical cancer cell migration and S100A4 protein expression, which were reduced in response to arctiin. Taken together, these results suggest that arctiin inhibits cervical cancer cell migration and invasion through suppression of S100A4 and the PI3K/Akt pathway.

Highlights

SiHa cells were significantly reduced by arctiin compared with the control. These results suggested that arctiin significantly reduced the cell migration and invasion of cervical cancer cells in a concentration-dependent manner
To determine the effect of S100A4 expression on cervical cancer cell migration, the results suggested that arctiin significantly reduced the cell migration and invasion of ceroverexpression vector of S100A4 (CS2-S100A4) was used
Various Chinese herbal medicines or herbal products have been investigated for the Various Chinese herbal medicines or herbal products have been investigated for the treatment of cervical cancer [22]; the anticancer effects of arctiin have been demonstrated treatment of cervical cancer [22]; the anticancer effects of arctiin have been demonstrated in in several studies

Summary

Introduction

As the fourth most common malignancy diagnosed in women worldwide, cervical cancer is a global health concern [1]. Patients with cervical cancer with metastasis have poor prognosis, with a median survival of 8–13 months [2]. The 5-year survival rate is 16.5% for metastatic cervical cancer, compared with 91.5% for localized cervical cancer [3,4]. Treatment options for patients with early-stage cervical cancer and locally advanced cervical cancer include surgery, chemotherapy, or radiotherapy. No standard treatment is available for patients with metastatic cervical cancer because of its heterogeneous manifestations [3]. Because treatment options for metastatic disease are limited, palliative treatment is the major consideration [2].

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Conclusion